Sequential treatment combining cladribine-based re-induction, myeloablative allogeneic HSCT, and prophylactic donor lymphocyte infusion: a promising treatment for refractory acute myeloid leukemia

Haowen Xiao, Li Li, Yan Pang, Yuanbin Wu, Zujun Jiang, Zenghui Liu, Jiulong Wu, Yang Xiao, Fen Huang, Qifa Liu, Hang Zhang, Yi Luo, He Huang

We describe the first multicenter prospective study to assess the efficacy, safety, and immune reconstitution of a novel sequential transplant approach in 24 patients with primary induction failure/relapsed acute myeloid leukemia (AML). The sequential regimen consisted of cladribine 5 mg/m2/day and cytarabine 2 g/m2/day for 5 days and mitoxantrone 7 mg/m2/day for 3 days, followed by myeloablative allogeneic hematopoietic stem cell transplantation (allo-HSCT) using intravenous busulfan (3.2 mg/kg/day) for 4 days and cyclophosphamide (60 mg/kg/day) for 2 days. Patients in CR without acute graft-versus-host disease at day + 90 received prophylactic donor lymphocyte infusion (pDLI). At the time of transplantation, a marrow blast infiltration > 20% or any level of circulating blasts was found in 62.5% of patients. The cumulative incidence of relapse at 2 years was 29.8%. Overall survival (OS) was 74.5% at 1 year and 56.5% at 2 years. Leukemia-free survival (LFS) at 1 and 2 years was 62.5 and 50.5%, respectively. Multivariate analysis demonstrated that haploidentical related donor, pDLI, and experiencing chronic graft-versus-host disease (cGVHD) were protective from relapse. Total T cells and T cell subsets in peripheral blood recovered at 3 months post-HSCT. The expressions of immune checkpoints (cytotoxic T lymphocyte antigen 4 and programmed death 1) were extremely low in T cells over the first 1 year post-transplantation.